Microbial transformation studies are being conducted with highly active antitumor compounds isolated from nature. Microorganisms are being employed to accomplish selective chemical changes in the structures of such chemicals under the mild reaction conditions obtained in fermentations. Where appropriate, derivatives of microbial metabolites will be prepared and tested in suitable tumor test systems. Microbial transformations of natrual antitumor drugs will continue to be developed as a general method for: preparing quantities of potentially active metabolites; providing difficult-to-synthesize drug metabolites, the availability of which will facilitate drug metabolism studies in animals and man: elucidating potentially important pathways of metabolism of structurally complicated antitumor compounds; and establishing a working basis for further structure activity relationship studies on complex biologically active compounds from nature. Experiments are being pursued with the Vinca alkaloids, thalicarpine, d-tetrandrine, hernandaline derivatives, and other compounds. Structures of microbial metabolites are determined by chemical and spectral methods, and they will be examined for antitumor activity.